Having established that changes in nutrition markedly alter concentrations of free branched-chain amino acids in human plasma we proceeded to investigate the mechanism of these changes in rats. Our studies show that muscle tissue is principally responsible for the plasma changes. It appears that when the caloric intake becomes limited, the capacity of oxidative metabolism for branched-chain amino acids is promptly and selectively altered in the skeletal muscles. This alteration is in harmony with the supply of expendable metabolic fuels. Increased oxidation may be accompanied by accelerated breakdown of endogenous proteins if the caloric deficiency persists. The rise in plasma level of free branched-chain amino acids is a chemical marker for the induction of such phenomena. Further studies are underway to characterize the enzyme systems for the development of increased oxidation of branched-chain amino acid in the skeletal muscle.